Evaluation of the Effects of Human Cell Derived GM1 Ganglioside in the MPTP Lesioned Pre-clinical Model of Parkinson's Disease

Rapid Response Innovation Awards, 2012

Objective/Rationale: † † † † † ††

The objective of this study is to evaluate the effects of human cell derived GM1 (hGM1) ganglioside in the treatment of a pre-clinical model of Parkinsons disease (PD).† Previous studies have demonstrated the benefits of a GM1 (bGM1) product in pre-clinical models as well as human PD patients; bGM1 and placebo will serve as comparators to hGM1 in this study.†

Project Description: † † † † † ††

Pre-clinical models will receive treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a chemical shown to induce a Parkinsonian state in models, followed by two weeks of treatment with hGM1, bGM1 or placebo.† The effects of GM1 will be measured in levels of dopamine and its metabolite, neurotransmitters that are typically reduced in the Parkinsonian brain, as well as counts of specific neuron types within the substantia nigra, an area of the brain typically affected in PD.† Efficacy measures will be compared between the active treatment models, hGM1 and bGM1, as well as being compared to the PD control (MPTP with placebo), and the untreated control models.

If successful, hGM1 would represent a novel therapy for the management of PD.† Previous studies of bGM1 have shown benefits to PD symptoms with up to five years of treatment.† Further, some research has provided evidence suggesting a potential benefit in modifying the progression of PD in patients.† Advancement of hGM1 would provide a viable source for pharmaceutical grade GM1 to further explore the benefits of GM1 in this population.

Anticipated Outcome: † † † † †

This study intends to demonstrate statistically significant increases in the levels of dopamine and its metabolites, as well as the number of select neurons in the substantia nigra, following treatment with hGM1 in comparison with placebo.† This study would assume to produce comparable improvements in PD efficacy measures to those seen with bGM1 treatment.†